Eteplirsen is a medication used in the treatment of Duchenne muscular dystrophy (DMD). It is a type of antisense oligonucleotide drug developed by Sarepta Therapeutics. Eteplirsen works by helping to restore the production of dystrophin, a protein that is crucial for maintaining muscle integrity. In DMD, there is a mutation in the dystrophin gene, leading to a lack of functional dystrophin. By promoting the production of dystrophin, eteplirsen aims to slow down the progression of the disease.

Eteplirsen received accelerated approval from the U.S. Food and Drug Administration (FDA) in September 2016, based on data from a small clinical trial that showed an increase in dystrophin production in some patients. However, the approval was controversial and faced criticism due to the small size of the trial and the limited evidence of clinical benefit. Subsequent larger trials and real-world evidence studies have provided mixed results regarding the drug's efficacy.

Eteplirsen (Exondys 51) is the first treatment that has been approved for the treatment of specific types of Duchenne muscular dystrophy. It is an antisense oligonucleotide that targets exon 51 of mRNA resulting in its exclusion during further processing. It is therefore only indicated in patients with a confirmed mutation of the DMD gene.

Eteplirsen (Exondys 51)Uses:

• Duchenne muscular dystrophy:
  • It is indicated for the treatment of patients with Duchenne muscular dystrophy (DMD) who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping.

Eteplirsen (Exondys 51) Dose in Adults

Eteplirsen (Exondys 51) Dose in the treatment of Duchenne muscular dystrophy:

• Eteplirsen is a medicine for Duchenne muscular dystrophy. It's given through a vein in a dose of 30 milligrams per kilogram of body weight once a week.

Eteplirsen (Exondys 51) Dose in Children

Eteplirsen (Exondys 51) Dose in the treatment of Duchenne muscular dystrophy (DMD):

• For treating Duchenne muscular dystrophy (DMD) in boys aged 7 years and older, and adolescents, Eteplirsen is given through a vein at a dose of 30 milligrams per kilogram of body weight once a week. This dosage was used in clinical trials involving patients aged 7 to 13 years.

Pregnancy Risk Category: N

• No studies have been done in animals to see how Eteplirsen might affect reproduction.
• Also, research hasn't looked at how Eteplirsen works in females.

Eteplirsen use during breastfeeding:

• Whether eteplirsen passes into breast milk is uncertain.
• If you're considering breastfeeding while taking this medication, you should weigh the potential risk of the baby being exposed to the drug against the benefits of breastfeeding and the benefits of treatment for the mother.
• It's important to note that eteplirsen hasn't been studied specifically in females.

Dose in Kidney Disease:

• The manufacturer's instructions do not mention any changes in dosage for people with kidney problems.
• However, this is because the drug hasn't been studied specifically in individuals with kidney issues.

Dose in Liver disease:

• The manufacturer's instructions do not include any adjustments to the dosage for individuals with liver problems.
• This lack of adjustment is because the drug hasn't been specifically studied in people with liver impairment.

Side Effects of Eteplirsen (Exondys 51):

• Central nervous system:
  • Equilibrium disturbance
• Dermatologic:
  • Contact dermatitis
• Gastrointestinal:
  • Vomiting

Contraindications to Eteplirsen (Exondys 51):

The manufacturer's instructions do not mention any specific situations where the use of eteplirsen would be prohibited or considered unsafe.

Warnings and precautions

Hypersensitivity

• Some individuals may experience hypersensitivity reactions while using eteplirsen.
• These reactions can include symptoms like rash, hives, fever, flushing, coughing, difficulty breathing, bronchospasm (tightening of the airways), and low blood pressure.
• If such reactions occur, it's important to handle them properly.
• This might involve slowing down the rate of infusion or temporarily stopping the therapy.

Monitoring Parameters:

Monitor for hypersensitivity reactions.

How to administer Eteplirsen (Exondys 51)?

• IV Infusion: Eteplirsen is given through a vein (IV) as an infusion over 35 to 60 minutes. The infusion should be completed within 4 hours of dilution.

Hypersensitivity Reactions:

• Management: If hypersensitivity reactions occur, such as rash, fever, coughing, or difficulty breathing, consider slowing down the infusion rate or temporarily stopping the therapy.

IV Access:

• Flush IV Line: Before and after the infusion, flush the IV access line with normal saline (NS) solution to keep it clear and prevent blockages.
• Avoid Mixing: Do not mix eteplirsen with other medications or infuse other medications simultaneously through the same IV access line to prevent potential interactions.

Missed Dose:

• Prompt Administration: If a dose is missed, administer it as soon as possible after the scheduled time to maintain the treatment schedule and effectiveness.

Mechanism of action of Eteplirsen (Exondys 51):

• Eteplirsen works by attaching to a specific part of the dystrophin pre-messenger RNA (mRNA) called exon 51.
• This binding leads to the exclusion of exon 51 during the processing of mRNA.
• When exon 51 is skipped, it enables the production of a shorter form of the dystrophin protein.
• This truncated dystrophin protein, although incomplete, can still function to some extent, providing support to muscle cells in individuals with Duchenne muscular dystrophy.

Distribution:

• Volume of Distribution (V): 600 mL/kg dss (which stands for "days since start"), indicating the volume in which the drug appears to be distributed throughout the body over time.

Protein Binding:

• Eteplirsen binds to proteins in the blood to a moderate extent, with protein binding ranging from 6% to 17%.

Half-life Elimination:

• The half-life of elimination for eteplirsen is relatively short, lasting approximately 3 to 4 hours.
• This means that it takes this amount of time for half of the drug to be cleared from the body.

Time to Peak:

• The time it takes for eteplirsen to reach its peak concentration in the bloodstream is relatively quick, occurring approximately 1.1 to 1.2 hours after administration.

Excretion:

• Eteplirsen is primarily eliminated from the body through the kidneys, indicating that it is excreted in the urine.

International Brand Names of Eteplirsen:

• Exondys 51

Eteplirsen Brand Names in Pakistan:

Not available.